RESUMO

The giant reed (Arundo donax) is a fast-growing plant adapted to different climatic and soil conditions; although its origin is Asian, the species has spread throughout the world. During its development, it consumes three times more water than typical native vegetation and is responsible for changing the landscape of riparian areas; the high biomass productivity and the annual harvest period make this crop an alternative to produce and/or extract industrial bioproducts. The main objective of this research was to evaluate the feasibility of using giant reed in a bioprocess that produces enzymes by a solid-state fermentation experiment, four fungal species were tested (Aspergillus niger GH1, Aspergillus niger PSH, Trichoderma harzianum, and Rhizopus oryzae); enzyme activities were performed using reported methodologies varying only reaction volumes. The A. niger GH1 and PSH strains were the best adapted to the plant material, A. niger GH1 was capable to produce 4 of the 5 evaluated enzymes (cellulase-endoglucanase (174.39 ± 19.62 U/L), xylanase (1313.31 ± 39.25 U/L), invertase (642.22 ± 23.55 U/L), and polyphenol oxidase (6094.01 ± 306.54) while A. niger PSH was able to produce 3 of the 5 evaluated enzymes (cellulase-endoglucanase (147.09 ± 13.88 U/L), xylanase (1307.76 ± 31.40 U/L), and invertase (603.92 ± 3.14 U/L).

RESUMO

Constructed wetlands are environmental solutions that mitigate the impacts of urban effluents. It is unclear how the performance of these wastewater treatment plants (WWTP) is affected by climatic conditions. The dissipation of nutrients, suspended solids, and changes in dissolved oxygen were investigated on a monthly basis over two years (2018/2019) at six sampling points across a WWTP located in Esquel, Patagonia. It was predicted that climatic variables (rain pattern and air temperature) would affect the functioning and efficiency of the WWTP (i.e., via nutrient load mitigation and sediment retention). Rainfall and temporal patterns differed markedly between and throughout the two years, leading to a clear seasonality in the transformation of pollutants. Nitrate loads were significantly higher in 2018 than in 2019 suggesting some degree of operational failure, whereas ammonia levels in treated effluents were extremely high during both years, with marked peaks occurring during autumn 2018 and summer 2019. The WWTP was moderately successful (~36%) in reducing TSS contents during 2018 but was inefficient in 2019. Ammonia levels in receiving waters underwent dilution due to rains rather than due to adequate WWTP nutrient retention. In terms of nutrients, effluent values exceeded those established by governmental regulation during most months, but worsened during summer coinciding with low flows. This lack of predictability for the values of the treated effluent strongly jeopardizes the ecological integrity and biodiversity of the receiving stream.

Assuntos

RESUMO

In this study, we investigated the main constituent, the predominant class and biological activity of the essential oil extracted from the leaves of Pimenta dioica and the pattern of the major constituent against larvae in the third stage of Aedes aegypti. For this reason, we extracted the oil by hydrodistillation, identified its components by gas chromatography coupled with mass spectrometry (GC/MS) and calculated the lethal concentration (LC50) of the larvicidal activity using the Reed-Muench method. The results show that the oil consists mainly of eugenol, in which the phenylpropanoid class predominated and the lethal concentration, LC50, was 38.86 µg mL-1at a confidence level of 2.25 µg mL-1, while the eugenol standard presented LC5079.75 µg mL-1at a confidence level of 2.10 µg mL-1. Given the facts, we conclude that the oil is more active than the standard and that it has the potential to replace chemical larvicides.

En este estudio, investigamos el constituyente principal, la clase predominante y la actividad biológica del aceite esencial extraído de las hojas de Pimenta dioica y el patrón del constituyente principal contra las larvas en la tercera etapa de Aedes aegypti. Por este motivo, extrajimos el aceite por hidrodestilación, identificamos sus componentes mediante cromatografía de gases acoplada a espectrometría de masas (GC/MS) y calculamos la concentración letal (CL50) de la actividad larvicida mediante el método Reed-Muench. Los resultados muestran que el aceite está constituido principalmente por eugenol, en el que predominó la clase fenilpropanoide y la concentración letal, CL50, fue de 38,86 µg.mL-1 a un nivel de confianza de 2,25 µg.mL-1, mientras que el estándar de eugenol presentó CL50 79,75 µg.mL -1 a un nivel de confianza de 2,10 µg.mL-1. Dados los hechos, concluimos que el aceite es más activo que el estándar y que tiene el potencial de reemplazar los larvicidas químicos.

Assuntos

RESUMO

Hodgkin's lymphoma is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. Hodgkin's lymphoma is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.

Assuntos

RESUMO

El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.Hodgkin's lymphoma (HL) is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. HL is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

Assuntos

RESUMO

Un acontecimiento en la vida del doctor Carlos Juan Finlay Barrés motivó al Maestro Esteban Valderrama Peña a realizar la composición pictórica Triunfo de Finlay. La pintura representa al médico cubano exponiendo ante una comisión médica militar estadounidense, su teoría sobre el modo de contagio de la fiebre amarilla y el ente transmisor, el mosquito Aedes aegypti. Finlay había estudiado durante años la enfermedad sin que las autoridades coloniales reconocieran los resultados de sus investigaciones, a pesar de que la enfermedad causaba estragos en los militares españoles y la población. En 1898 la intervención norteamericana en la guerra de los cubanos contra el colonialismo español, generó la necesidad de sanear la Isla y crear condiciones higiénicas favorables para la estancia de las tropas norteñas. El general y médico Leonard Wood fijó su atención en la teoría de Finlay y solicitó al gobierno de su país especialistas para verificarla. Fue enviada una comisión dirigida por el mayor Walter Reed, cirujano del ejército y catedrático de bacteriología de la Facultad de Medicina Militar en Washington, para confirmarla. En la pintura, el artista representó la reunión de Finlay con la comisión norteña. El presente trabajo destaca la trascendencia de la obra, su valor estético y la integración del arte, la historia, la medicina y la ciencia. Se propone incluir su estudio como parte del trabajo educativo dirigido a fomentar la cultura general en la formación de los profesionales de la salud(AU)

One event for Doctor Carlos J. Finlay Barrés was the motive for the oil painting composition named "Triumph of Finlay" by Master of Art Esteban Valderrama Peña. The picture shows Finlay presenting his theory about the transmission of yellow fever by mosquitoes to the US Army Yellow Fever Commission. He had conceived a new infection way able to explain the propagation of the illness, and added the possibility of their scientific confirmation by experimental method. In 1898 the US army took place in the Cuban`s fighting against the Spanish colonialism. This circumstance beginning the need to improve the sanitary condition in the Island to create favorable hygienic conditions to the stay of the troops. The Military Governor of the Island, general and physician Leonard Wood took Finlay´s theory as center of his attention. He requested the government of his country experts to verify it. One commission heading for Major Walter Reed was sent. Reed was a surgeon of the army and professor of bacteriology in Military Medicine Faculty in Washington. After experimentally investigation, the commission could confirm Finlay´s theory. Valderrama´s picture shows the meeting of Finlay with the experts. This article has like objective to give emphasis about this pictorial by its importance for the Cuba´s medicine and the science history in Cuba. By the esthetic value that contains it must be included in the educational labor towards the preparation the professionals of the health. It is useful for contributing with the general culture integrating art, history, medicine and science(AU)

Assuntos

RESUMO

RESUMO O objetivo desta pesquisa foi a avaliação dos custos de implantação (CAPEX) e de operação (OPEX) de diferentes alternativas de desaguamento e higienização de lodo, em Estações de Tratamento de Esgoto (ETEs) com reatores anaeróbios de manto de lodo (UASB) e pós-tratamento aeróbio, visando fornecer subsídios para Estudos de Concepção. As tecnologias consideradas foram: leitos de secagem, centrífugas, wetlands construídos para lodo (WCL), estabilização alcalina prolongada (EAP) e secagem térmica. Curvas de custo para vazões de esgoto entre 5 e 750 L.s−1 foram elaboradas, desconsiderando-se os custos de aquisição de área e destinação final do lodo. Verificou-se que o CAPEX das centrífugas pode ser inferior ao dos leitos de secagem para ETEs com vazões acima de 80 L.s−1. Porém, ao considerar-se o OPEX, os leitos se mantêm mais econômicos. Também foi avaliada uma alternativa mista, de leitos de secagem e centrífugas em paralelo, mas seus custos mostraram-se mais elevados que cada opção isoladamente. Os WCL apresentaram CAPEX superior ao das centrífugas para ETEs acima de 120 L.s−1, mas foi mantida a alternativa mais econômica de desaguamento quando considerado CAPEX + OPEX. Quanto à higienização, a secagem térmica apresentou CAPEX inferior ao da EAP para ETEs acima de 500 L.s−1. Porém, ao se considerar o OPEX, essa se manteve mais onerosa até 750 L.s−1, mesmo considerando-se o aproveitamento do biogás gerado nos reatores UASB.

ABSTRACT This research assessed the implementation costs (CAPEX) and the operational costs (OPEX) of different sludge dewatering and disinfection alternatives, considering WWTP with UASB reactors and aerobic post-treatment, aiming to provide resources for Conception Studies. The following technologies were considered: Drying Beds, Centrifuges, Sludge Drying Reed Beds (SDRB), Alkaline Stabilization Process (ASP), and Heat Drying. Cost functions for wastewater flows ranging from 5 to 750 L.s−1 were elaborated, while disregarding area acquisition and sludge final disposal costs. It was determined that the Centrifuge's CAPEX could be lower than the Drying Bed's for WWTPs inflows above 80 L.s−1. Nonetheless, Drying Beds remained cheaper when OPEX was considered. A hybrid alternative with Drying Beds and Centrifuges in parallel was evaluated, but their combined costs remained higher than each option considered individually. Moreover, SDRB's CAPEX was higher than the Centrifuge's for WWTPs above 120 L.s−1, but the former remained the cheapest dewatering alternative when considered CAPEX + OPEX. Finally, Heat Drying had lower CAPEX than ASP for WWTPs above 500 L.s−1. Nonetheless, considering OPEX, the former remained more expensive up to 750 L.s−1, even when considering fully UASB biogas reclamation.

RESUMO

Resumen El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.

Abstract Hodgkin's lymphoma is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. Hodgkin's lymphoma is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

RESUMO

Throughout the time of the early settlement and development of North America, there were frequent epidemics of Yellow Fever. It is thought that ships transporting captured Africans likely conveyed both major vectors, the Aedes aegypti mosquito and the RNA Yellow Fever virus from Africa to North America. Infected ships landing in port cities resulted in epidemics that proved impossible to control with conventional interventions. Walter Reed and the U.S. Army Commission solved the mystery of the mode of Yellow Fever transmission. Reed and his co-workers not only proved the mosquito the vector of transmission but did so by constructing focused research questions leading to cleverly devised experiments that resulted in definitive answers. The results of their research not only proved that the mosquito transmitted the disease but disproved the other proposed modes of transmission. In nearly all respects, Reed's experiments are an excellent paradigm for addressing clinical research questions today.

Assuntos

RESUMO

Background: Pretreatment of lignocellulosic biomass is essential for using it as a raw material for chemical and biofuel production. This study evaluates the effects of variables in the chemical pretreatment of the Arundo biomass on the glucose and xylose concentrations in the final enzymatic hydrolysate. Three pretreatments were tested: acid pretreatment, acid pretreatment followed by alkaline pretreatment, and alkaline pretreatment. Results: The amounts of glucose and xylose released by the enzymatic hydrolysis of the Arundo biomass obtained from acid pretreatment ranged from 6.2 to 19.1 g/L and 1.8 to 3.1 g/L, respectively. The addition of alkaline pretreatment led to a higher yield from the enzymatic hydrolysis, with the average glucose concentration 3.5 times that obtained after biomass hydrolysis with an acid pretreatment exclusively. The use of an alkaline pretreatment alone resulted in glucose and xylose concentrations similar to those obtained in the two-step pretreatment: acid pretreatment followed by alkaline pretreatment. There was no significant difference in 5-hydroxymethylfurfural, furfural, or acetic acid concentrations among the pretreatments. Conclusion: Alkaline pretreatment was essential for obtaining high concentrations of glucose and xylose. The application of an alkaline pretreatment alone resulted in high glucose and xylose concentrations. This result is very significant as it allows a cost reduction by eliminating one step.

Assuntos

RESUMO

This essay documents and examines the historical circumstances and events surrounding the discovery of the mode of transmission of yellow fever virus in Cuba. Close scrutiny of the articles published by Walter Reed and his colleagues in 1900, 1901 and 1902 reveals their limitations as historic documents. Fortunately, other sources of information from that period survive in letters and documents written by individuals involved in the quest for the mode of transmission. Examination and comparison of those sources of information unveiled a fascinating story which reveals that misunderstandings engendered by published articles accorded merit where it was not fully due.

Assuntos

RESUMO

O linfoma é uma neoplasia originária do sistema linfático, a partir de células linfocitárias. A sintomatologia mais comum é febre, tosse, sudorese noturna, perda de peso, fraqueza e linfoadenopatia indolor. A etiologia ainda permanece desconhecida, tendo sido relacionada ao vírus Epstein-Barr. O diagnóstico se baseia na visualização das células de Reed-Sternberg. O esquema adriamicina, bleomicina, vinblastina e dacarbazina (ABVD) ainda é o tratamento preconizado, associado ou não à radioterapia. Relatamos um caso de linfoma de Hodgkin de apresentação atípica, cujo diagnóstico só foi possível por esplenectomia.(AU)

The lymphoma is a cancer of the lymphatic system originating from lymphocyte cells. The most common symptoms are fever, cough, night sweats, weight loss, weakness, and painless lymphadenopathy. The etiology remains unknown, having been related to the Epstein Barr virus. The diagnosis is based on visualization of Reed Sternberg cells. The adriamycin, bleomicin, vinblastine and dacarbazine (ABVD) regimen is still the preferred treatment, with or without radiation therapy. We report a case of Hodgkin's lymphoma of atypical presentation, the diagnosis of which was only possible through splenectomy.(AU)

Assuntos

RESUMO

Los leiomiomas son tumores infrecuentes, los piloleiomiomas son el tipo clínico más común y puede ser solitario o múltiple; este último puede ser esporádico o familiar. Presentamos un caso clínico de piloleiomiomas múltiples en dorso, en un paciente joven, a quien se le realizaron estudios para descartar una patología asociada.

Leiomyomas are rare tumors, piloleiomyomas are the most common clinical type and can be solitary or multiple which can be sporadic or familial. We report a case of multiple piloleiomyomas in the back of a young patient, in which studies were performed to rule out pathology associated.

RESUMO

O nevo de Spitz pigmentado consiste em uma lesão melanocítica benigna com características peculiares. Geralmente, melanoma é considerado no diagnóstico diferencial desta lesão, bem como o nevo de Reed. A dermatoscopia representa uma parte relevante da abordagem diagnóstica e, portanto, ela permite um estudo mais eficiente dessas lesões dermatológicas. O presente relato de caso é sobre uma paciente com dois nevos de Spitz pigmentados de localização no tronco e história familial de melanoma, no qual a dermatoscopia associada à histopatologia foram cruciais para o diagnósticos das lesões.

Assuntos

RESUMO

Los leiomiomas son tumores infrecuentes, los piloleiomiomas son el tipo clínico más común y puede ser solitario o múltiple; este último puede ser esporádico o familiar. Presentamos un caso clínico de piloleiomiomas múltiples en dorso, en un paciente joven, a quien se le realizaron estudios para descartar una patología asociada.(AU)

Leiomyomas are rare tumors, piloleiomyomas are the most common clinical type and can be solitary or multiple which can be sporadic or familial. We report a case of multiple piloleiomyomas in the back of a young patient, in which studies were performed to rule out pathology associated.(AU)

RESUMO

Human fumarase (HsFH) is a well-known citric acid cycle enzyme and is therefore a key component in energy metabolism. Genetic studies on human patients have shown that polymorphisms in the fumarase gene are responsible for diseases such as hereditary leiomyomatosis and renal cell cancer. As a first step in unravelling the molecular basis of the mechanism of fumarase deficiency in genetic disorders, the HsFH gene was cloned in pET-28a, heterologously expressed in Escherichia coli, purified by nickel-affinity chromatography and crystallized using the vapour-diffusion technique. X-ray diffraction experiments were performed at a synchrotron source and the structure was solved at 2.1 Šresolution by molecular replacement.

Assuntos

RESUMO

La guía está dirigida al equipo de la salud que atiende directamente a los pacientes, pero también indirectamente a quienes toman decisiones administrativas, tanto en el medio hospitalario como en las aseguradoras, pagadores del gasto y en las políticas de salud. Pretende lograr un diagnóstico oportuno y tratamiento adecuado de los pacientes pediátricos con LH. La guía está limitada a la detección temprana, diagnóstico, tratamiento y seguimiento de la población diana. La presente Guía dará recomendaciones para el manejo de pacientes con LH por parte del personal de salud especializado en oncología, onco-hematología, hematología pediátrica y a todo el personal involucrado en los niveles de atención III y IV del SGSS para el manejo integral del paciente.

Assuntos

RESUMO

Disminuir la variabilidad injustificada en el manejo diagnóstico y terapéutico especializado. Identificar campos clínicos y económicos de linfoma de Hodgkin pediátrico que necesitan investigación. Centralizar la atención especializada en instituciones de tercer o cuarto nivel de niños, niñas y adolescentes con sospecha diagnóstica para su confirmación, y tratamiento.

Assuntos

RESUMO

Este estudo apresenta achados microscópicos do nevo pigmentado de células fusiformes, designado como nevo de Reed, os quais resultaram de exames microscópicos realizados em múltiplos cortes de lesão de pele. Apresenta ainda a revisão de literatura pertinente. Os achados clínicos e microscópicos são consistentes com os dados da literatura descritos, originariamente, por Reed e colaboradores. O nevo de Reed é uma lesão melanocítica benigna, que, no entanto, pode ser equivocadamente identificada como um melanoma malígno. As lesões melanocíticas que podem ser confundidas com melanoma malígno devem ser avaliadas cuidadosamente, a fim de obter-se um diagnóstico acurado, e seguir-se a conduta pertinente.

This paper presents the findings of microscopic studies of the PigmentedSpindle-cell Nevus, called Nevus of Reed, carried on multiple sections of skin lesion. It presents, as well, a review of the related literature. The clinical andmicroscopic findings coincide with those originally described by Reed andcolleagues. The Nevus of Reed is a benign melanocytic lesion, which, however,can be easily misdiagnosed as a malignant melanoma. Therefore, in case of suchlesions, all efforts should be made to render an accurate diagnosis, and thus, toprovide the adequate therapy.

Assuntos

RESUMO

Introdução. O linfoma de Hodgkin (LH) é uma neoplasia caracterizada por uma minoria de elementos neoplásicos, chamados de células de Reed-Sternberg (CRS) e suas variantes, e uma mistura de células inflamatórias que infiltram a massa tumoral, incluindo linfócitos, eosinófilos, plasmócitos, histiócitos e fibroblastos. Estudos clínicos e biológicos nos últimos 20 anos demonstraram o LH é verdadeiramente um linfoma, constituído por duas entidades distintas: o LH forma predominância linfocitária nodular (LHPLN) e o LH Clássico (LHC). Além disso, forneceram evidências de que as CRS são derivadas de células B do centro germinativo que sofreram mutações defeituosas ("crippling" mutations) de seus genes de imunoglobulina, tornando-os não funcionais. Ao contrário de linfócitos normais, que entram em apoptose por não produzirem imunoglobulina ou por produzir imungolobulinas com baixa afinidade antigênica, as CRS, por mecanismos ainda não completamente elucidados, são capazes de escapar deste processo de morte celular programada. Diversos genes ligados à regulação da apoptose, como os genes da família bcl-2, fas, fasL, c-FLIP, NFkappaB, têm sido investigados no LH, alguns dos quais parecem ter influência na evolução clínica dos pacientes. O papel desempenhado pelo vírus de Epstein-Barr (EBV) no bloqueio da apoptose no LH também tem sido intensamente estudado. O óxido nítrico (ON) é uma molécula diatômica cuja participação na regulação de numerosos processos que governam a carcinogênese, como o estímulo à profileração, ocorrência de mutações, bloqueio de apoptose, indução da angiogênese e ocorrência de metástases, tem sido intensamente estudada. O ON é produzido por uma família de enzimas denominadas sintases do óxido nítrico (NOS). Um aumento da expressão dos genes que codificam NOS e da produção de ON tem sido demonstrado em diversas neoplasias humanas, incluindo cânceres de mama, estômago, cólon, bexiga, próstata, pulmão e neoplasias hematopoiéticas. Objetivos. O objetivo deste estudo é analisar a expressão das sintases do óxido nítrico (NOS1, NOS2), da nitrotirosina (evidência indireta da produção de óxido nítrico) e de proteínas associadas a apoptose (bcl-2, bax, p53, fas e fasL) no LHC, para testar a hipótese de que a produção de NOS e ON pelas CRS está envolvida na regulação defeituosa da apoptose nesta neoplasia. Foi estudada ainda a possível correlação destas moléculas com a infecção pelo EBV observada no LHC. Finalmente, pesquisou-se a capacidade das células L&H do LHPLN de produzir NOS e ON. Material e métodos. Blocos de parafina contendo material conservado em formalina de 238 casos de LHC foram selecionados do arquivo do Departamento de Patologia do Centro de Tratamento e Pesquisa Hospital do Câncer A C Camargo, São Paulo, Brasil, no período de 1980 a 2000. Foram excluídos casos com material insuficiente para realização do estudo, biópsias de recidiva e casos HIV-positivos. Após revisão histopatológica e, quando necessário, imunoistoquímica, foram submetidos a estudo imunoistoquímico utilizando anticorpos para NOS1, NOS2, nitrotirosina, bcl-2, bax, p53, fas, fasL e LMP1. Foi realizada ainda hibridização in situ com sonda contra o transcrito EBER-1 do vírus de Epstein-Barr. As lâminas foram analisadas e os resultados submetidos à análise estatística. Foram selecionados ainda 7 casos de LHPLN, que, após confirmação diagnóstica, foram submetidos a estudo imunoistoquímico utilizando anticorpos para NOS1, NOS2 e nitrotirosina. Resultados. Dos 238 casos iniciais de LHC, 171 foram selecionados para análise. A expressão de NOS1 e de NOS2 foi observada em 42.1% e 55% dos casos, respectivamente. A expressão de nitrotirosina foi observada em 18.7% dos casos. As expressões de bcl-2, bax, p53, fas, fasL e LMP1 foram observadas, respectivamente, em 35.1%, 44.4%, 44.4%, 93,6%, 5.8% e 49.7% dos casos. O transcrito EBER-1 foi detectado em 46.8% dos casos. Foram observadas associações estatisticamente significativas entre fas e sexo masculino (p=0.032), EBV (LMP-1 e EBER) e sexo masculino (p<0.0001), EBV (LMP-1 e EBER) e subtipo histológico celularidade mista (p<0.0001), EBV e estadios avançados (LMP-1, p=0.0459; EBER, p=0.011), EBV (EBER) e sintomas B (p=0.0481), bax e p53 (p=0.036), bax e fasL (p=0.046), NOS1 e p53 (p=0.006), bax e NOS2 (p=0.022); e entre bcl-2 e NOS2 (p=0.034). Correlação inversa foi observada entre EBV (LMP-1) e NOS2 (p=0.018) , e entre EBV e bcl-2 (LMP-1, p=0.002; EBER, p=0.006). Observou-se ainda uma diminuição da sobrevida global associada à forte expressão de NOS2 (p=0.0098). A forte expressão de NOS2 pelas CRS também foi fator associado a um pior prognóstico em casos tratados com o esquema quimioterápico MOPP/ABVD (p=0.0003). Com relação ao LHPLN, observou-se expressão de NOS1 e NOS2 pelas células L&H em 42.9% e 71.4% dos casos, respectivamente. Não se observou a expressão de nitrotirosina. Conclusões. Os resultados do presente estudo demonstraram a capacidade das CRS de expressarem NOS e produzirem ON, assim como de expressarem genes produtores de proteínas reguladoras do ciclo celular. As correlações observadas entre NOS e as proteínas associadas a apoptose sugerem o envolvimento das NOS e do ON no controle deste processo. Observou-se ainda que a expressão de NOS2 está associada a uma menor sobrevida global nos casos de LHC. Com relação ao LHPLN, demonstrou-se que as células L&H são capazes de produzir NOS1 e NOS2. Não foi possível demonstrar, entretanto, a produção de nitrotirosina..

Background. Hodgkin' s lymphoma (HL) is a neoplasm composed by a minority of neoplastic cells, named Hodgkin and Reed-Stemberg (H-RS) cells, set in an inflammatory background consisting of lymphocytes, eosinophils, neutrophils, histiocytes, plasma cells and fibroblasts. Clinicai and biological studies over the past 20 years have concluded that HL is indeed a lymphoma, divided into 2 distinct entities: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (CHL ). Furthermore, they gave evidence that H-RS cells are derived from germinai center B cells with rearranged immunoglobulin genes bearing crippling mutations. Unlike normal B lymphocytes, which suffer apoptosis when failing to produce immunoglobulins, or producing low-antigenic affinity immunoglobulins, H-RS cells, by tnechanisms not fully understood, are capable of escaping apoptotic cell death. Many apoptotic regulators, such as bcl-2 family members, fas, fasL, c-FLIP, and NFkappaB, have been investigated in HL, some of which appearing to influence the clinicai outcome o f HL patients. The role o f EBV in the resistance to apoptotic cell death o f H-RS cells has also been under study. Nitric oxide (NO) is a diatomic molecule involved in multiple steps of carcinogenesis, such as DNA mutations, proliferation, blockage of apoptosis and angiogenic stimulation. NO is produced by a family of enzymes known as the nitric oxide synthases (NOS). NOS gene overexpression and NO production have been observed in many human tumors from various sites such as the breast, stomach, colon, bladder, prostate, lung and the haematopoietic system. Objective. The purpose o f this study was to analyze the role o f NOS (NOS 1, NOS2) and apoptosis-associated proteins expression in HL, to test the hypothesis that NOS and NO production by H-RS cells are involved in the deffective apoptotic program of this neoplasm. We also investigated the role of EBV expression in HL on NOS expression and NO production. Finally, we investigated if L&H cells of NLPHL could produce NOS and NO. Material and methods. 238 retrospective cases of HL, diagnosed between 1980 and 2000, were retrieved from the archives o f the Departamento de Patologia do Centro de Pesquisa do Hospital do Câncer A C Camargo. Cases without enough formalin-fixed and paraffin-embedded tis sue to run the immunohistochemical (IH C) reactions, relapse biopsies and HIVassociated HL were excluded. Histological diagnosis was revised, with the use of immunostains when necessary. Immunostains with antibodies against NOS 1, NOS2, nitrotyrosine, bcl-2, bax, p53, fas, fasL and LMP1 were performed. Cases were also tested for EBV presence using in situ hybridization for EBV early RNAs (EBER). We also selected 7 cases diagnosed as NLPHL, which were tested for NOS 1, NOS2 and nitrotyrosine expression. Results. A total o f 171 cases from the original 23 8 cases collected were available for analysis. NOS 1 and NOS 2 expression were detected in 42.1% and 55% of the cases, respectively. Nitrotyrosine expression was observed in 18.7% ofthe cases. Bcl-2, bax, p53, fas, fasL and LMP1 expression were observed in 35.1 %, 44.4%, 44.4%, 93,6%, 5.8% e 49.7o/o of the cases, respectively. The EBER-1 transcript was detected in 46.8% of the cases. Significant associations were established between fas and male gender (p=0.032), EBV (LMP-1 e EBER) and male gender (p<0.0001), EBV (LMP-1 e EBER) and mixed cellularity subtype (p<0.0001), EBV and late stages ofthe disease (LMP-1, p=0.0459; EBER, p=0.011 ), EBV (EBER) and B symptons (p=0.0481), bax and p53 (p=0.036), bax and fasL (p=0.046), NOS1 and p53 (p=0.006), bax and NOS2 (p=0.022); and between bcl-2 e NOS2 (p=0.034). An inverse correlation was observed between EBV (LMP-1) and NOS2 (p=0.018), and between EBV and bcl-2 (LMP-1, p=0.002; EBER, p=0.006). Strong NOS2 expression was associated with a shorter overall survival (p=0.0098). It also predicted a poor prognosis in those cases treated with MOPP/ ABVD (p=0.0003). Regarding NLPHL, NOS1 and NOS2 expression by L&H cells was detected in 42.9% and 71.4% ofthe cases, respectively. Nitrotyrosine expression was not detected. Conclusions. We conclude that H-RS cells are capable of expressing NOS and producing NO. They are also capable of producing many apoptosisassociated proteins. The correlations observed between NOS and apoptosisassociated proteins suggest that NOS and NO are involved in the defective apoptotic program of HL. Strong NOS2 expression is associated with a poor outcome in HL. We also conclude that L&H cells ofNLPHL express NOSI and NOS2. Nitrotyrosine expression, however, could not be established.

Assuntos